tbuckley/cabot-search huggingface dataset:
Efficacy and safety of tislelizumab combined with lenvatinib and FOLFOX4-HAIC in conversion therapy of middle-advanced stage hepatocellular carcinoma (HCC): A real-world retrospective study.
Authors: Kai Tan, Xiaojun He, Hu Zhang, Shoujie Zhao, Chenyu Gong, Yaoyao Zhao, Haiyan Nan, Li Zang, Zhonghua Luo, Jikai Yin, Xilin Du
Journal: Journal of Clinical Oncology (2023)

e16137 Background: Conversion therapy achieve tumor downstaging and provide middle-advanced stage HCC patients with opportunities for radical resection. Lenvatinib combined with immune checkpoint inhibitors (ICIs) and FOLFOX-HAIC has shown high conversion success rates. This study aimed to evaluate the efficacy and safety of tislelizumab combined with lenvatinib and FOLFOX4-HAIC as first-line conversion therapy in this population. Methods: Between April, 2021, and April, 2022, we retrospectively analyzed clinical data of HCC patients with BCLC stage B or C who underwent tislelizumab combined with lenvatinib and FOLFOX4-HAIC. The primary outcome included objective response rate (ORR), disease control rate (DCR), conversion resection rate (CRR) and treatment-related adverse events (TRAEs). Data were expressed as median(range). Results: A total of 18 patients (17 male, 1 female) completed conversion therapy assessment until the last follow-up time (December 27, 2022). The patients were characterized with a median age of 55.5 years (37-72), body mass index 24.9(19.8-33.9), 1 patient with BCLC stage B, 16 patients with BCLC stage C, and 1 patient with HCC postoperative recurrence with intrahepatic metastasis. According to mRECIST criteria, tumor shrinkage was observed in all patients, with an ORR of 94.4% (17/18, including 61.1% [11/18] complete response), DCR of 94.4% (17/18), and median time to response(mTTR) of 1.4 months (0.7-3.0). Successful conversion was observed in 11 (61.1%) of 18 patients per mRECIST. As of cut-off date, the actual CRR and pathological complete response(pCR) were 38.9% (7/18) and 57.1% (4/7), respectively. No surgical deaths occurred, and at the last follow-up review, there was disease free survival in all patients after operation. With a follow-up time of 20.7 months, median progression-free survival (PFS) and overall survival (OS) were not reached, with a 3- and 6-month progression-free survival rate of 94.4% and 83.3%. During the follow-up period, 6 patients developed disease progression with a median time to progression (mTTP) of 5.4 months (1-6.7), of whom 3 died due to disease progression. Most common TRAE was aspartate aminotransferase (AST) increased (16 patients, 88.9%). Grades ≥3 TRAEs occurred in 12 patients (66.7%), with only one grade 4 TRAE (AST increased). All TRAEs were tolerable and manageable. Conclusions: Tislelizumab combined with lenvatinib and FOLFOX4-HAIC showed high conversion rate and acceptable toxicity in the treatment of middle-advanced stage HCC, suggesting that this combination could be considered as a new conversion strategy in this population.
Neutrophil extracellular trap as a predictive marker to cisplatin-based chemotherapy for patients with muscle-invasive bladder cancer.
Authors: Bing-Qing Shang, Zhaoru Gu, Wang Qu, Rui-Yang Xie, Jie Wu, Ai-Ping Zhou, Jianzhong Shou
Journal: Journal of Clinical Oncology (2023)

e16600 Background: Cisplatin-based chemotherapy is the recommended therapy for muscle-invasive bladder cancer (MIBC), in both the neoadjuvant and first-line settings. However, the efficacy of MIBC for chemotherapy is only about 40%~60%. Patients without clear benefits from cisplatin-based chemotherapy still suffer from the potential toxicity, possibly missing the timing for other effective treatments. Therefore, predictors of therapy response are urgently needed. Neutrophils form neutrophil extracellular traps (NETs), a network structure, and growing evidence indicated that it could be a prognostic and predictive marker in cancer. In bladder cancer, NETs were involved in radio-resistance, but the predictive role of chemotherapy is unclear. This study constructed a NET-related signature that predicted chemotherapy efficacy for MIBC patients. Methods: Transcriptome datasets were obtained from the transurethral resection of bladder tumor (TURBT) and metastatic lesion specimens. A dataset (GSE169455) of 149 MIBC patients who received preoperative cisplatin-based chemotherapy (neoadjuvant or induction) was enrolled for the training cohort. We used the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model to select candidate molecules based on the 250 NETs-initial biomarkers collected from the literature, and further developed a NETs-associated signature score (NETs-score) for therapeutic response prediction. The dataset reported by Taber A et al. of 96 MIBC patients who received cisplatin-based chemotherapy (neoadjuvant or first-line) was used as a validation cohort. Immunohistochemistry (IHC) was conducted to evaluate the potential role of NET-related genes in 51 patients who received neoadjuvant chemotherapy at our center from 2012 to 2019. Results: We constructed the NETs-score with 11 NETs-related genes by the LASSO Cox model. A higher NET score was observed in non-responders compared to responders in the training cohort (P&lt;0.001). These results were confirmed in the validation cohort (P=0.006). Moreover, high NETs-score indicated reduced recurrence-free survival (RFS) [HR=2.07, 95% CI (1.26-3.40), P=0.003], cancer-specific survival (CSS) [HR=1.87, 95% CI (1.12-3.12), P=0.014], and overall survival (OS) [HR=1.83, 95% CI (1.13-2.94), P=0.012] among MIBC patients. Furthermore, in the IHC cohort, citrullinated histone H3 (H3Cit) as a hallmark of NETs, was an independent predictor of chemotherapy resistance as determined by the multivariate logistic regression analysis [OR=5.94, 95% CI 1.20–45.50, P=0.045]. Conclusions: In conclusion, our study suggested that NET was a predictive and prognostic biomarker for MIBC patients with cisplatin-based chemotherapy. [Table: see text]
Disparities in accessing open notes at a comprehensive cancer center.
Authors: Elena R. Cutting, Euyhyun Lee, Ge Zhang, Kathryn A. Gold
Journal: Journal of Clinical Oncology (2023)

e18507 Background: Patient use of open access medical notes can promote understanding of and engagement in disease management, in turn improving patient satisfaction, trust, medication adherence and clinical outcomes. Previous studies have shown that racial minorities were less likely to utilize personal health records online, as were patients with lower incomes compared to those with higher incomes. The CURES Act, enacted as of April 5 2021, is a national policy that requires healthcare providers to give patients access to the information and notes available on their own electronic medical registry. Given the recency of this legislation, little is known about who is accessing this information or how we can help it to be more widely accessible. Methods: We extracted demographic data available for all patients with an outpatient oncology encounter at UCSD between 1/1/21-12/31/21. Data available included age, gender, ethnicity, preferred language, and type of insurance. Mann-Whitney U test and Fisher’s exact test were used to compare continuous and categorical variables between the two groups, respectively. This analysis was approved by the UCSD ACQUIRE committee and met criteria for IRB excusal. Results: There were 22,419 patients who met inclusion criteria, 21,892 (97.3%) of whom were registered on MyChart and 4,114 (18.4%) of whom had accessed an oncology note. There was no significant difference in age or gender between those who did or did not access notes. Patient race, ethnicity, preferred language, and insurance type were all significantly different between groups (p&lt;0.001), with those who were non-White, Hispanic, Spanish speaking, or on Medicaid less likely to access their notes through OpenNotes. Conclusions: There are significant differences in the demographics of patients who do and do not access notes. Targeted outreach efforts (e.g., translation efforts) may help in making access to open notes more equitable. [Table: see text]
A phase 2 study of HLX07 as monotherapy or combination therapy in patients with locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma.
Authors: Jing Huang, Yun Liu, Tao Wu, Zhen-yang Liu, Jin Zhou, Yuan Yuan, Mudan Yang, Bo Liu, Zhenbo Tan, Wu Zhuang, Jiayan Chen, Yanqing Liu, Haoyu Yu, Qingyu Wang, Jun Zhu
Journal: Journal of Clinical Oncology (2023)

4029 Background: Esophageal cancer is one of the most common cancers worldwide with esophageal squamous cell carcinoma (ESCC) being the predominant histological subtype. Most patients are diagnosed at the advanced stage, and the prognosis remains poor. About 40–84% of ESCC cases showed overexpression of EGFR which was related to shorter overall survival and disease-free survival, indicating that treatment targeting EGFR could be a new strategy. This study aimed to evaluate the efficacy and safety of HLX07, a novel recombinant humanized anti-EGFR monoclonal antibody (mAb), as monotherapy or combination therapy in patients with locally advanced, unresectable/metastatic ESCC. Methods: In this open-label, multicenter phase 2 study, patients aged 18–75 years with histologically or cytologically confirmed locally advanced, unresectable/metastatic ESCC or esophageal adenosquamous carcinoma were enrolled. Patients with no prior systemic antitumor therapy were assigned to group A and given HLX07 1000 mg plus serplulimab 200 mg (anti-PD-1 mAb) and chemotherapy (5-FU 2400 mg/m 2 + cisplatin 50 mg/m 2 ), Q2W IV. Patients who had failed first-line immuno-chemotherapy combination or at least two lines of other systemic antitumor therapy were assigned to group B and given HLX07 monotherapy (1000 mg Q2W IV). The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) assessed by an independent radiological review committee and investigators per RECIST v1.1. Secondary endpoints included other efficacy measures, safety, pharmacokinetics, immunogenicity, and biomarker explorations. Results: As of February 4, 2023, 49 patients were enrolled in group A (n=30) and group B (n=19), with a median age of 64.5 and 59.0 years, respectively. 26 (86.7%) patients in group A and all patients in group B were male. The median follow-up duration was 2.9 months, and the preliminary efficacy was presented. Among the 42 efficacy evaluable patients (29 in group A and 13 in group B), investigator-assessed ORRs were 55.2% (95% CI 35.7–73.6%) and 23.1% (95% CI 5.0–53.8%) in the respective groups. Investigator-assessed median PFSs were not reached in group A and 1.5 months (95% CI 1.2–not evaluable) in group B. 15 (50.0%) patients in group A and 5 (26.3%) in group B had grade ≥3 treatment-emergent adverse events (AEs). AEs of special interest were observed in 16 (53.3%) and 11 (57.9%) patients, respectively, most commonly rash (43.3% vs 47.4%) and hypomagnesemia (33.3% vs 36.8%). No drug-related death was reported. Conclusions: The encouraging antitumor activity and manageable safety profile support further development of HLX07 as a new treatment option for patients with advanced ESCC, both in first-line and late-line settings. Clinical trial information: NCT05221658 .
A phase 2, randomized, open-label study comparing the effects of darolutamide versus enzalutamide monotherapy on serum testosterone levels in patients with hormone-naive prostate cancer: ARAMON study.
Authors: Xin Gao, Matthew Raymond Smith, Howard I. Scher, Frank Verholen, Patrick Adorjan, Manjari Dissanayake, Andrew Leonard Laccetti
Journal: Journal of Clinical Oncology (2023)

TPS5111 Background: Darolutamide is a structurally distinct and highly potent androgen receptor inhibitor with low blood–brain barrier penetration. In the phase 3 ARAMIS study (NCT02200614) of patients with nonmetastatic castration-resistant prostate cancer, treatment with darolutamide significantly improved metastasis-free survival and overall survival versus placebo, with a favorable safety profile. The incidences of central nervous system adverse events (AEs; e.g. falls, memory impairment, and depression) showed a ≤2% difference between the darolutamide and placebo groups. Fatigue was the only AE with an incidence of &gt; 10% for darolutamide (13.2% vs 8.3% for placebo). In a separate neuroimaging study of healthy volunteers, cerebral blood flow was not altered in patients treated with darolutamide but was significantly reduced in brain areas related to cognition in patients treated with enzalutamide. Furthermore, it is postulated that the low blood–brain barrier penetration of darolutamide may result in lower serum testosterone elevations than those seen with enzalutamide, with the potential of leading to fewer associated feminizing AEs. The objective of ARAMON (NCT05526248) is to compare the effect of darolutamide and enzalutamide monotherapy on post-treatment testosterone levels in patients with hormone-naive prostate cancer experiencing biochemical recurrence after definitive treatment for localized disease. Methods: ARAMON is a two-stage, open-label, phase 2 study of patients with histologically or cytologically confirmed adenocarcinoma of the prostate who have biochemical recurrence after radical primary prostatectomy or radiation therapy, with a prostate-specific antigen (PSA) doubling time of ≤20 months, baseline serum testosterone &gt; 150 ng/dL, and Eastern Cooperative Oncology Group performance status 0/1. During a 52-week lead-in phase, 25 patients will receive darolutamide 600 mg twice daily. If criteria based on serum testosterone increase from baseline to Week 12 are met, the study will proceed to a 52-week randomized phase in which the effects of darolutamide (600 mg twice daily, n = 20) will be compared with the effects of enzalutamide (160 mg once daily, n = 20). The primary endpoint of both phases is the change in serum testosterone level from baseline to Week 12. Secondary endpoints of the randomized phase include the change in serum testosterone levels from baseline to Weeks 24 and 52; PSA at Weeks 4, 12, 24, 36, and 52; changes in blood levels of markers for glucose, lipid metabolism, and endocrine function related to sex hormones; safety; and quality of life. Safety will be assessed through AE monitoring. The first of the 25 planned patients in the lead-in phase was enrolled on January 13, 2023. Clinical trial information: NCT05526248 .
Total pancreatectomy: Experience within an integrated health care system.
Authors: Amber Chang, Hyunjee V. Kwak, Peter D Peng, George Kazantsev, Austin L Spitzer, CK Chang
Journal: Journal of Clinical Oncology (2023)

e16269 Background: Total pancreatectomy (TP) is most used for pancreatic adenocarcinoma (PC) but also for main duct intra-ductal papillary mucinous neoplasm. The authors report on a retrospective study of 61 patients who underwent TP in an integrated healthcare system. Methods: A retrospective review was performed of all patients treated with TP between January 2012 and December 2022. Patient demographics, tumor characteristics, treatment modalities, and mean overall survival (OS) were evaluated. Results: An intra-operative positive pancreatic neck margin for cancer or high-grade dysplasia was the most common indication for TP in 77% (47/61) of patients. The mean OS for patients with pancreatic cancer was 18 months, however, patients with a pre-op diagnosis of IPMN had a mean OS of 50 months. Multivariate analysis of PC without IPMN showed that neoadjuvant and NPH insulin were associated with a decrease in overall survival ( p&lt; .05). Overall HbA1c were higher in patients after one year after surgery for patients taking NPH (8.6) as opposed to an insulin pump (7.6) or Lantus (7.6) but not significant ( p= .346). Mean OS for patients with PC and type of insulin used was statistically significant at 24.4 months vs 13.1 months respectively for Lantus vs NPH ( p= .033). Conclusions: Conversion to TP for positive neck margins did not improve survival in patients who receive neoadjuvant chemotherapy but may be helpful in patients with IPMN. Blood sugar control after one year was similar among the various indication groups as well the type of insulin use. Although Lantus insulin was associated with improved overall survival for patients with pancreatic cancer, the exact reason is unclear and requires further studies.
Overall survival (OS) by response to first-line (1L) induction treatment with atezolizumab (atezo) + platinum/gemcitabine (plt/gem) vs placebo + plt/gem in patients (pts) with metastatic urothelial carcinoma (mUC): Updated data from the IMvigor130 OS final analysis.
Authors: Enrique Grande, Aristotelis Bamias, Matt D. Galsky, Eiji Kikuchi, Ian D. Davis, José A. Arranz, Arash Rezazadeh, Xavier Garcia del Muro, Se Hoon Park, Ugo De Giorgi, Boris Alekseev, Marina Mencinger, Kouji Izumi, Javier Puente, Jian-Ri Li, Chooi Lee, Sandrine Bernhard, Alan Nicholas, Julie Telliez, Maria De Santis
Journal: Journal of Clinical Oncology (2023)

4503 Background: For pts without disease progression during 1L plt-based chemotherapy (chemo), maintenance immunotherapy is a new mUC treatment option. IMvigor130 was a global, randomized Phase III study evaluating 1L atezo + plt/gem (Arm A) vs atezo monotherapy (Arm B) and placebo + plt/gem (Arm C) in patients with mUC (Galsky Lancet 2020). The final analysis showed that improved OS in Arm A vs Arm C of the intention-to-treat (ITT) population did not reach statistical significance (Galsky ASCO GU 2023). Here we report a post hoc analysis examining OS outcomes by response during atezo/placebo + chemo “induction” based on the final OS analysis. Methods: For Arms A and C, per protocol, investigators pre-specified the type of chemo pts received (gem + either cisplatin [cis] or carboplatin [carbo]), which was also a randomization stratification factor. Pts without progressive disease (PD) were allowed to continue atezo or placebo after 4 to 6 cycles of plt/gem. This post hoc analysis evaluated post-induction (Wk 18) OS in pts who completed 4 to 6 cycles of chemo followed by ≥1 dose of atezo or placebo and who had a best response of at least stable disease (SD) without PD at any time (up to and including Wk 18 tumor assessment). Post-progression OS was evaluated in pts who had PD at any time (up to and including Wk 18 tumor assessment). OS analyses by type of chemo were also performed. Multivariable Cox proportional hazards models were used, with HRs adjusted for known prognostic factors (and response for non-PD pts) and stratified by enrollment stage. Results: The time from last pt randomized to the data cutoff (Aug 31, 2022) was 49 mo (overall ITT population). OS improvements favoring Arm A vs C appeared greater for pts treated with cis than with carbo. In the cis subgroup, OS rates at 36 mo were 47% (Arm A) and 34% (Arm C) for pts who achieved at least SD during induction. Additional efficacy data are shown. Conclusions: In this post hoc analysis, the initial response to induction therapy did not seem to impact OS outcomes. Consistent with prior analyses, these data suggest that cis-treated pts may derive a greater benefit from the addition of atezo than carbo-treated pts. Clinical trial information: NCT02807636 . [Table: see text]
The number of lymph nodes examined as a poor prognosis factor in stage II and stage III colon cancer patients undergoing curative surgery.
Authors: JEONGSEOK JEON, Lingjie Shen, Yitak Kim, Hyunwook Kim, Anna J. van Gestel, Yoon Dae Han, Dai Hoon Han, Seng Chan You, Joong Ahn, Sangjoon Shin, Gijs Geleijnse, Han Sang Kim
Journal: Journal of Clinical Oncology (2023)

3612 Background: The number of lymph nodes (LN) examined is a key factor in determining the stage of colorectal cancer. Over the past 20 years, the examination of fewer than 12 LN has been regarded as a poor prognosis. However, surgical procedures and pathologic examination improvements have increased the number of LN examined. This raised the question of reassessing the best cutoff point for staging colon cancer patients undergoing curative surgery. Methods: We reviewed a total of 3,126 eligible patients with stage II-III colon cancer collected from the Yonsei Cancer Center Registry (YCC) database between 2005 and 2015. As a validation cohort, we used clinicodemographic data from 9,604 patients with stage II-III colon cancer identified by the Netherlands Cancer Registry (NCR) between 2006 and 2015. The hazard ratio (HR) obtained from Cox-proportional regression was used to investigate the effect of LNs' yield on 6-year overall survival (OS). The optimal LN yield was evaluated by analyzing every cutoff from 3 to 165. We used the Kaplan-Meier method to compare the effect of higher vs. lower optimal LN yield on a 6-year OS. Univariate and multivariate Cox regressions were conducted. Results: The proportion of patients with fewer than 12 LN examined dramatically decreased between 2005 and 2015 (17.4% in 2005 vs. 0.6% in 2015, P&lt; 0.001). Based on the 12 LN examined as the conventional cutoff number, there was no significant association between 6-year OS and LN yield in all stages II-III patients (HR = 1.21, P= 0.116; n = 3,126), stage II (HR = 1.39, P= 0.068; n = 1,570), and stage III (HR = 1.18, P= 0.297; n = 1,557) colon cancer. Interestingly, a higher cutoff of 20 LN examined was associated with a significant increase in 6-year OS in all patients (HR = 1.51, P&lt; 0.001 in patients with LN examined less than 20). Multivariate Cox-proportional hazard regression showed a significant decrease in 6-year OS in stage II (HR = 1.39, P= 0.026) and stage III (HR = 1.54, P&lt; 0.001) with less than 20 LN yield. Consistent with the result in the YCC database, less than 20 of LN yield was associated with poorer 6-year OS in stage II-III patients (HR = 1.25, P&lt; 0.001; n = 9,604), stage II (HR = 1.43, P&lt; 0.001; n = 4,689), and stage III (HR = 1.13, P= 0.007; n = 4,915) in the NCR, respectively. Conclusions: Less than 20 LN examined is associated with a poorer prognosis in patients with surgically treated colon cancer, compared to the current cutoff value of 12. Further validation of re-evaluating criteria on the inadequacy of LN retrieval in high-risk stage II colon cancer is warranted.